A thorough knowledge of the structure and function of regeneration nerve terminals is basic to our understanding of the molecular events that underlie the regenerative process. Studies of regenerating synapses may also give insight into the mechanisms involved in the formation of nerve terminals that occurs during normal development. During the past several years I have studied thin amphibian skeletal muscles and autonomic ganglia in which individual synapses on live muscle fibers and nerve cells can be seen with appropriate optical systems. In these preparations, one can place microelectrodes directly upon nerve terminals or at known distances from them; the very same synapses studied physiologically can then be examined by a variety of histological and histochemical techniques including electron microscopy. The structural and functional analysis of single synapses has already led to a number of new findings regarding the release of transmitter from nerve terminals and the chemosensitivity of postsynaptic membranes. I now propose to examine the formation of the same synapses, specifically those in the skeletal muscle and the cardiac ganglion of the frog, during the regeneration of their severed presynaptic axons. My objectives during the next 5 years will be: 1) to work out the steps in the formation of regenerating nerve terminals in skeletal muscle; 2) to correlate the development of neuromuscular transmission with the structural development of the regenerating nerve endings; 3) to examine the role played by the Schwann cell and muscle fiber in the formation of the nerve terminal; and 4) to compare the regeneration of nerve terminals at the neuromuscular junction to the regeneration of synapses on autonomic nerve cells in the frog's cardiac ganglion.